Cited by 3,114T-cell and B-cell ImmunologyCancer Immunotherapy and BiomarkersImmunotherapy and Immune Responses

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Molecular mechanisms of T cell co-stimulation and co-inhibition

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Chen, Lieping, Flies, Dallas B.·2013·Nature Reviews Immunology

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Abstract

Co-stimulatory and co-inhibitory receptors have a pivotal role in T cell biology, as they determine the functional outcome of T cell receptor (TCR) signalling. The classic definition of T cell co-stimulation continues to evolve through the identification of new co-stimulatory and co-inhibitory receptors, the biochemical characterization of their downstream signalling events and the delineation of their immunological functions. Notably, it has been recently appreciated that co-stimulatory and co-inhibitory receptors display great diversity in expression, structure and function, and that their functions are largely context dependent. Here, we focus on some of these emerging concepts and review the mechanisms through which T cell activation, differentiation and function is controlled by co-stimulatory and co-inhibitory receptors.

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Lafferty, K. J. & Cunningham, A. J. A. New analysis of allogeneic interactions. J. Immunol. 112, 436–437 (1975). Lafferty and Cunningham extended the Bretscher and Cohn two-signal model to suggest that T cells require two signals for activation.

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Authors: Chen, L., & Flies, D. B.
Affiliations: Yale Cancer Center (US)
University of New Mexico (US)
Corresponding author: Chen, Lieping
ORCID: Chen, Lieping
Flies, Dallas B.
Venue: Nature Reviews Immunology
Publisher: Springer Science and Business Media LLC
Published: 2013-03-08
Volume: 13
Issue: 4
Pages: 227-242
ISSN: 1474-1733 (ISSN-L)
1474-1741
DOI: 10.1038/nri3405
PMC: PMC3786574
OpenAlex: W2130473166
Cited by: 3,114
References: 135
Citations by year: 2026: 148 · 2025: 258 · 2024: 259 · 2023: 276 · 2022: 305 · 2021: 312 · 2020: 310 · 2019: 250 · 2018: 275 · 2017: 238 · 2016: 195 · 2015: 148 · 2014: 101 · 2013: 35
FWCI: 13.52
Type: journal article
Language: en
Update notices: erratum (2013-06-05)
Open access: green
europepmc.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature reviews. Immunology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Melanoma Research Alliance
National Cancer Institute (CA 97085, CA 16359, CA121974, CA86721, R01CA097085, CA142779, R01CA085721, R01CA142779, P50CA121974, P30CA016359)
National Institute of Allergy and Infectious Diseases (T32AI089704, R01AI072592, AI72592, T32AI007247)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: T cell costimulation, T cell co-inhibition, costimulatory receptors, co-inhibitory receptors, T cell receptor signaling, T cell activation, T cell differentiation, immune checkpoint molecules
MeSH terms: Humans, Lymphocyte Activation, Receptors, Antigen, T-Cell, T-Lymphocytes, Signal Transduction, CD28 Antigens, B7-1 Antigen, Models, Immunological, B7-2 Antigen, Receptors, Tumor Necrosis Factor, Member 14

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Molecular mechanisms of T cell co-stimulation and co-inhibition

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